Patients with well-documented chronic non-A, non-B hepatitis are being evaluated to determine the long-term natural history of this common form of chronic liver disease. A cohort of such patients is available to evaluate experimental therapies for this disease. To date nine patients with chronic non-A, non-B hepatitis have been treated with recombinant human alpha interferon for periods ranging from 2 months to one year. Seven of the nine patients have shown a dramatic decrease in serum aminotransferase levels during therapy, their levels falling from values 3 to 10 times the upper limit of the normal range to normal (6 patients) or near-normal (1 patient). Follow-up liver biopsies have been obtained from two patients, both of which demonstrate marked improvement in the hepatitis disease activity (a decrease in both inflammation and hepatocellular necrosis). The dose and schedule of administration of interferon are currently being adjusted to identify the optimal regime to achieve maximal benefit (as monitored by serum aminotransferase levels) with minimal side effects and discomfort. The optimum dose appears to be 2 million units (mu) given three times per week. A prospective, randomized, placebo-controlled trial of a six month course of human alpha interferon in patients with chronic non-A, non-B hepatitis is planned.